Fibrinogen plays a central role in hemostasis and blood coagulation in health and disease. Pathophysiologic consumption of fibrinogen has long been recognized as intrinsic to the thrombotic diseases and is a striking intermediary pathogenetic mechanism in disseminated intravascular coagulation, microangiopathic hemolytic anemia and other selected diseases. The pathological consumption of fibrinogen may be associated with enzymatic conversion to fibrin and subsequent physiological cleavage, all of which is associated with systematic structural and specific immunochemical modification of fibrinogen. We propose to investigate the molecular and pathogenetic properties of fibrinogen, fibrin, soluble complexes and cleavage fragments, and to relate these observations to the structure and function of these modified molecules and fragments using specific quantitative immunochemical markers. The role of molecular modification, complex formation and cleavage, and the cellular and immune response of the host, in the pathogenesis of injury will be explored. The possible role of these new and quantitatively assessable molecular expressions in disease will be investigated in experimental animals and in clinical disease.